This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a randomized, multicenter study for patients with measurable, stage IV melanoma. This study will: (a) estimate whether the addition of helper peptides to class I MHC-restricted peptides augments T-cell responses to the Class I MHC-restricted peptides, (b) characterize the phenotype of vaccine-induced CD8+ T cells, (c) determine the helper T-cell response to each helper peptide, (d) obtain preliminary data on whether booster vaccination every three months may maintain immune responses to a peptide vaccine, and (e) obtain preliminary data on whether cellular immune responses to a 12-epitope peptide vaccine correlates with clinical outcome.